1. Field of the Invention
The present invention relates generally to the field of medicinal chemistry. More particularly, it concerns chemotherapeutic compounds capable of binding to DNA and/or crossing the blood brain barrier.
2. Description of Related Art
The anthracyclines daunorubicin and doxorubicin (DOX) are some of the more commonly used chemotherapeutic antibiotics. The anthracyclines achieve their cytotoxic effect by several mechanisms, including inhibition of topoisomerase II; intercalation between DNA strands, thereby interfering with DNA and RNA synthesis; production of free radicals that react with and damage intracellular proteins and nucleic acids; chelation of divalent cations; and reaction with cell membranes. The wide range of potential sites of action may account for the broad efficacy as well as the toxicity of the anthracyclines (Young et al., 1985). Although there are marked differences in the clinical use of daunorubicin and doxorubicin, their chemical structures differ only by a single hydroxyl group on C14. Previous modifications of these compounds have been undertaken to improve their selectivity towards specific tumors types (U.S. Pat. Nos. 6,673,907, 7,109,177, and 7,557,090 and PCT Publication WO 2008/029294). In particular, brain cancers can be difficult to treat as many compounds cannot easily cross the blood brain barrier (Pardridge, 1999; Bickel, et al., 2001). As such, new compounds which show increased activity and/or ability to cross the blood brain barrier are clinically needed.